Gene therapy research targets mutations for brittle bone disease

Researchers at the UW and elsewhere have developed a targeted gene therapy that eliminates in adult stem cells the genetic mutations associated with brittle bone disease. Results of the study were published in the Feb. 20 issue of the journal Science.

Brittle bone disease, or osteogenesis imperfecta, is caused by mutations in two collagen genes, COL1A1 and COL1A2. Patients with the condition have skeletal abnormalities, and often suffer from easily broken bones.

Researchers led by Drs. David Russell, associate professor of medicine in the Division of Hematology, and Joel Chamberlain, a senior fellow in hematology and the study’s lead author, developed a method of viral vector gene targeting that could treat a specific gene within a cell. They collaborated with Dr. Peter Byers, professor of pathology and medicine and prominent brittle bone disease researcher, to try to use that gene therapy to treat the disorder.

They took stem cells from the bone marrow of patients with the disease and used the targeted gene therapy to disrupt the mutations. The collagen protein produced by the stem cells had improved assembly and stability necessary for bone strength, and the cells were capable of forming bone when implanted later in mice.

The researchers hope the method of targeting a specific gene in its normal position on a chromosome will help not just in the treatment of brittle bone disease, but also in other genetic disorders.

The group also included researchers from Children’s Hospital and Regional Medical Center in Seattle, the University of Michigan, and Shriner’s Hospital in Portland.